Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques

Diogo M. Magnani, Thomas F. Rogers, Nicholas J. Maness, Nathan D. Grubaugh, Nathan Beutler, Varian K. Bailey, Lucas Gonzalez-Nieto, Martin J. Gutman, Núria Pedreño-Lopez, Jaclyn M. Kwal, Michael J. Ricciardi, Tereance A. Myers, Justin G. Julander, Rudolf P. Bohm, Margaret H. Gilbert, Faith Schiro, Pyone P. Aye, Robert V. Blair, Mauricio A. Martins, Kathrine P. Falkenstein, Amitinder Kaur, Christine L. Curry, Esper G. Kallas, Ronald C. Desrosiers, Pascal J. Goldschmidt-Clermont, Stephen S. Whitehead, Kristian G. Andersen, Myrna C. Bonaldo, Andrew A. Lackner, Antonito T. Panganiban, Dennis R. Burton () and David I. Watkins ()
Additional contact information
Diogo M. Magnani: University of Miami Leonard M. Miller School of Medicine
Thomas F. Rogers: The Scripps Research Institute
Nicholas J. Maness: Tulane National Primate Research Center
Nathan D. Grubaugh: The Scripps Research Institute
Nathan Beutler: The Scripps Research Institute
Varian K. Bailey: University of Miami Leonard M. Miller School of Medicine
Lucas Gonzalez-Nieto: University of Miami Leonard M. Miller School of Medicine
Martin J. Gutman: University of Miami Leonard M. Miller School of Medicine
Núria Pedreño-Lopez: University of Miami Leonard M. Miller School of Medicine
Jaclyn M. Kwal: University of Miami Leonard M. Miller School of Medicine
Michael J. Ricciardi: University of Miami Leonard M. Miller School of Medicine
Tereance A. Myers: Tulane National Primate Research Center
Justin G. Julander: Utah State University
Rudolf P. Bohm: Tulane National Primate Research Center
Margaret H. Gilbert: Tulane National Primate Research Center
Faith Schiro: Tulane National Primate Research Center
Pyone P. Aye: Tulane National Primate Research Center
Robert V. Blair: Tulane National Primate Research Center
Mauricio A. Martins: University of Miami Leonard M. Miller School of Medicine
Kathrine P. Falkenstein: Tulane National Primate Research Center
Amitinder Kaur: Tulane National Primate Research Center
Christine L. Curry: University of Miami Leonard M. Miller School of Medicine
Esper G. Kallas: University of São Paulo
Ronald C. Desrosiers: University of Miami Leonard M. Miller School of Medicine
Pascal J. Goldschmidt-Clermont: University of Miami Leonard M. Miller School of Medicine
Stephen S. Whitehead: National Institutes of Health
Kristian G. Andersen: The Scripps Research Institute
Myrna C. Bonaldo: Instituto Oswaldo Cruz, Fiocruz
Andrew A. Lackner: Tulane National Primate Research Center
Antonito T. Panganiban: Tulane National Primate Research Center
Dennis R. Burton: The Scripps Research Institute
David I. Watkins: University of Miami Leonard M. Miller School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

Date: 2018
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DOI: 10.1038/s41467-018-04056-4

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